title: Down-regulation of transcobalamin receptor TCblR/CD320 by siRNA inhibits cobalamin uptake and proliferation of cells in culture.
abstract: The clinical phenotype of cobalamin (Cbl) deficiency is dictated by the essential role of this vitamin in two key enzymatic reactions. Multiple proteins and receptors participate in the absorption, transport and delivery of this vitamin to tissue cells. Cellular uptake of Cbl is mediated by transcobalamin (TC), a plasma protein and a transmembrane receptor (TCblR) with high affinity for TC saturated with Cbl. Knockdown of TCblR with siRNA results in decreased TC-Cbl uptake. The ensuing Cbl deficiency leads to an increase in doubling time and decreased proliferation of these cells. The study confirms the seminal role of this receptor in the cellular uptake of Cbl and its down-regulation as a potential strategy to inhibit proliferation of cancer cells.
authors.affiliation: School of Graduate Studies, SUNY-Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Shao-Chiang
authors.initials: SC
authors.lastname: Lai
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
authors.forename: Edward V
authors.initials: EV
authors.lastname: Quadros
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C538894:CD320 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D014805:Vitamin B 12